Il segnale serotoninergico è importante nel controllo del rimodellamento osseo in risposta alle sollecitazioni meccaniche nel ratto

There is increasing experimental and clinical evidence that serotonin (5-HT) may regulate bone metabolism. In fact, on bone cells have been detected functional receptors for 5-HT, 5-HT transporters and the tryptophan hydroxylase, a key enzyme for the synthesis of 5-HT from tryptophan (TRP). It is well known that depressive disorders involve 5-HT system and that low bone mass is frequent in depressed patients. Since low level of physical activity, characteristic of depressed patients, is also associated to low bone mass, it remains to be clarified the relative contribution of reduced 5-HT tone or disuse in the detrimental effect of depression on bone mass. Therefore, the aim of this study was to investigate the effects of reduced 5-HT tone, induced by chronic TRP depletion, in the control of bone mass and bone remodelling in condition of osteopenia induced by physiological movement restraint in the rat. For this purpose, rats received a TRP-free diet or a standard control diet for 60 days. To induce a physiological movement restraint, all rats were housed in single small size cages with a floor area of cm2 370 their motor activity was diminished. Bone mass, mineral content (BMC) and density (BMD) were measured by DXA and pQCT in the femur. Bone metabolic markers included markers of bone resorption (urinary deoxypyridinoline, DPD) and markers of bone formation (serum osteocalcin, OC). In control diet-fed rats both femoral BMC and BMD, as measured by DXA, decreased with time due to reduced movement. TRP-free diet significantly worsened the osteopenia induced by movement restraint. The reduction of both BMC and BMD either in control diet rats or in TRP-free diet rats was higher in femoral methaphysis than in femoral diaphysis. At the end of the experimental period, pQCT analysis of femoral methaphysis showed that TRP-free diet resulted in a significant reduction of BMC on total bone, trabecular, cortical and subcortical bone in comparison with control-diet fed rats. Due to decrease in BMC and cortical thickness, the femoral strength strain index (SSI) was reduced. These effects are due to a negative shift in the balance between bone formation and resorption with a significant reduction in bone formation as evidenced by a reduction of OC and by the impairment of the Wnt/b-catenin pathway, which enhances the sensitivity of osteoblasts/osteocytes to mechanical loading. The present data extend our knowledge on the role of 5-HT in the regulation of bone mass. In particular, our findings demonstrate that 5-HT is involved in the control of the anabolic response of bone to mechanical loading